tbuckley/cabot-search huggingface dataset:
Folliculin inactivation and cutaneous leiomyosarcoma in Birt-Hogg-Dubé syndrome
Authors: William Fostier, Georgie Holt, James Sampson, Neil Rajan
Journal: British Journal of Dermatology (2023)

Cutaneous leiomyosarcoma (cLMS) is a rare soft tissue sarcoma where the genetic drivers implicated in carcinogenesis are not completely characterized despite extensive genomic profiling. The presentation of cLMS in Birt-Hogg-Dube (BHD) syndrome, which is caused by heterozygous pathogenic variants in FLCN, adds to our mechanistic understanding of the pathogenesis of cLMS and implicates FLCN loss. In this report, we demonstrate loss of heterozygosity (LOH) of FLCN in BHD cLMS, providing novel genetic evidence that a subset of cLMS may be driven by FLCN loss and that cLMS is an infrequent but recurrent element of the BHD phenotype.
Defining drug/drug class refractoriness vs lines of therapy in relapsed/refractory multiple myeloma
Authors: Utkarsh Goel, Charalampos Charalampous, Prashant Kapoor, Moritz Binder, Francis K. Buadi, David Dingli, Angela Dispenzieri, Amie Fonder, Morie A. Gertz, Wilson I. Gonsalves, Suzanne R. Hayman, Miriam A. Hobbs, Yi L. Hwa, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Rahma M. Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Journal: Blood Cancer Journal (2023)

Defining drug
The gene mutation landscape of acute myeloid leukemia cell lines and its exemplar use to study the BCOR tumor suppressor
Authors: Valentina Pettirossi, Alessandra Venanzi, Ariele Spanhol-Rosseto, Gianluca Schiavoni, Alessia Santi, Luisa Tasselli, Marta Naccari, Valentina Pensato, Alessandra Pucciarini, Maria Paola Martelli, Hans Drexler, Brunangelo Falini, Enrico Tiacci
Journal: Leukemia (2023)
Unravelling the enigma of siRNA and aptamer mediated therapies against pancreatic cancer
Authors: Zhe Liu, Neha Parveen, Urushi Rehman, Aisha Aziz, Afsana Sheikh, Mohammed A. S. Abourehab, Wei Guo, Junhao Huang, Zhenning Wang, Prashant Kesharwani
Journal: Molecular Cancer (2023)

Pancreatic cancer (PC) is a fatal disease that has a poor 5-year survival rate. The poor prognosis can be attributed to both troublesome detections at the initial stage, which makes the majority of the treatment options largely unsuccessful and leads to extensive metastasis, as well as to its distinct pathophysiological characteristics, such as rich desmoplastic tumours bounded by dysplastic and hypo perfused vessels restricting the mobility of therapeutic agents. Continued attempts have been made to utilise innovative measures for battling PC to increase the therapeutic effectiveness of therapies and overcome their cytotoxicity. Combined cancer targeting and gene silencing approach has shown improved outcomes in patients' survival rates and quality of life, offering a potential solution to therapeutic complications. It particularly targets various barriers to alleviate delivery problems and diminish tumour recurrence and metastasis. While aptamers, a type of single-stranded nucleic acids with strong binding affinity and specificity to target molecules, have recently surfaced as a viable PC strategy, siRNA can interfere with the expression of certain genes. By concurrently suppressing genes and boosting targeted approach, the cocktail of siRNA/Aptamer and other therapeutic drugs can circumvent the multi-drug resistance phenomena. Additionally, combination therapy with additive or synergistic effects can considerably increase the therapeutic efficacy of anti-cancer medications. This study outlines the primary difficulties in treating PC, along with recent developments in siRNA/Aptamer mediated drug delivery to solve the major hiccup of oncology field.
Two pan-SARS-CoV-2 nanobodies and their multivalent derivatives effectively prevent Omicron infections in mice
Authors: Honghui Liu, Lili Wu, Bo Liu, Ke Xu, Wenwen Lei, Jianguo Deng, Xiaoyu Rong, Pei Du, Lebing Wang, Dongbin Wang, Xiaolong Zhang, Chao Su, Yuhai Bi, Hua Chen, William J. Liu, Jianxun Qi, Qingwei Cui, Shuhui Qi, Ruiwen Fan, Jingkun Jiang, Guizhen Wu, George F. Gao, Qihui Wang
Journal: Cell Reports Medicine (2023)

With the widespread vaccinations against coronavirus disease 2019 (COVID-19), we are witnessing gradually waning neutralizing antibodies and increasing cases of breakthrough infections, necessitating the development of drugs aside from vaccines, particularly ones that can be administered outside of hospitals. Here, we present two cross-reactive nanobodies (R14 and S43) and their multivalent derivatives, including decameric ones (fused to the immunoglobulin M [IgM] Fc) that maintain potent neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after aerosolization and display not only pan-SARS-CoV-2 but also varied pan-sarbecovirus activities. Through respiratory administration to mice, monovalent and decameric R14 significantly reduce the lung viral RNAs at low dose and display potent pre- and post-exposure protection. Furthermore, structural studies reveal the neutralizing mechanisms of R14 and S43 and the multiple inhibition effects that the multivalent derivatives exert. Our work demonstrates promising convenient drug candidates via respiratory administration against SARS-CoV-2 infection, which can contribute to containing the COVID-19 pandemic.
The<i>European Respiratory Journal</i>: the ERS flagship heads for the next frontier
Authors: James D. Chalmers, Don D. Sin
Journal: European Respiratory Journal (2023)

<b>The new <i>European Respiratory Journal</i> Chief Editor James Chalmers and Deputy Chief Editor Don Sin discuss the future direction of the journal and highlights from 2022</b>https://bit.ly/3vrJ9ex
Midline 1 interacting protein 1 promotes cancer metastasis through FOS-like 1-mediated matrix metalloproteinase 9 signaling in HCC
Authors: Yung-Tuen Chiu, Abdullah Husain, Karen Man-Fong Sze, Daniel Wai-Hung Ho, Eliana Mary Senires Suarez, Xia Wang, Eva Lee, Hoi-Tang Ma, Joyce Man-Fong Lee, Lo-Kong Chan, Irene Oi-Lin Ng
Journal: Hepatology (2023)

Background and Aims: Understanding the mechanisms of HCC progression and metastasis is crucial to improve early diagnosis and treatment. This study aimed to identify key molecular targets involved in HCC metastasis. Approach and Results: Using whole-transcriptome sequencing of patients’ HCCs, we identified and validated midline 1 interacting protein 1 (MID1IP1) as one of the most significantly upregulated genes in metastatic HCCs, suggesting its potential role in HCC metastasis. Clinicopathological correlation demonstrated that MID1IP1 upregulation significantly correlated with more aggressive tumor phenotypes and poorer patient overall survival rates. Functionally, overexpression of MID1IP1 significantly promoted the migratory and invasive abilities and enhanced the sphere-forming ability and expression of cancer stemness-related genes of HCC cells, whereas its stable knockdown abrogated these effects. Perturbation of MID1IP1 led to significant tumor shrinkage and reduced pulmonary metastases in an orthotopic liver injection mouse model and reduced pulmonary metastases in a tail-vein injection model in vivo . Mechanistically, SP1 transcriptional factor was found to be an upstream driver of MID1IP1 transcription. Furthermore, transcriptomic sequencing on MID1IP1-overexpressing HCC cells identified FOS-like 1 (FRA1) as a critical downstream mediator of MID1IP1. MID1IP1 upregulated FRA1 to subsequently promote its transcriptional activity and extracellular matrix degradation activity of matrix metalloproteinase MMP9, while knockdown of FRA1 effectively abolished the MID1IP1-induced migratory and invasive abilities. Conclusions: Our study identified MID1IP1 as a regulator in promoting FRA1-mediated-MMP9 signaling and demonstrated its role in HCC metastasis. Targeting MID1IP1-mediated FRA1 pathway may serve as a potential therapeutic strategy against HCC progression.
Outcome of patients with HCC and liver dysfunction under immunotherapy: a systematic review and meta-analysis
Authors: Ismael El Hajra, Marco Sanduzzi-Zamparelli, Víctor Sapena, Sergio Muñoz-Martínez, Ezequiel Mauro, Neus Llarch, Gemma Iserte, Alejandro Forner, José Rios, Jordi Bruix, María Reig
Journal: Hepatology (2023)

Background and Aims: Immunotherapy-based regimes have changed the management of HCC. However, evidence of efficacy in patients with impaired liver function is unknown. This systematic review and meta-analysis assesses survival of HCC patients and liver dysfunction treated with immunotherapy-based regimens. Methods: Systematic review and meta-analysis of original articles or abstracts reporting survival of HCC patients treated with immunotherapy according to liver function between 2017 and 2022. Overal survival (OS) according to restricted mean survival time (RMST) and median OS, and hazard ratio (HR) of Child-Pugh B or B/C versus Child-Pugh A were assessed while considering the line of treatment. Results: Of the 2218 articles considered, 15 articles recruiting 2311 patients were included. Of these, 639 (27.7%) were Child-Pugh B and 34 (1.5%) C. RMST was 8.36 (95% CI, 6.15–10.57; I 2 =93%) months, estimated from 8 studies. The HR was reported in 8 studies for survival between Child-Pugh B versus Child-Pugh A and metanalysis disclosed a 1.65 HR (95% CI,1.45–1.84; I 2 =0% heterogeneity; p = 0.45). Treatment line data were available for 47% of the patients and 3 studies included patients treated with atezolizumab-bevacizumab in the first line. Conclusions: The high heterogeneity across studies reflects the incapacity of the current evidence to support the indication of immunotherapy in HCC patients with relevant liver dysfunction. It is mandatory to report complementary information to Child-Pugh classification such as prior liver decompensation, use of concomitant medication to control ascites, or signs of clinically significant portal hypertension to allow better patient stratification in future studies.
Advancements in nanoparticle-based treatment approaches for skin cancer therapy
Authors: Leli Zeng, B. H. Jaswanth Gowda, Mohammed Gulzar Ahmed, Mohammed A. S. Abourehab, Zhe-Sheng Chen, Changhua Zhang, Jia Li, Prashant Kesharwani
Journal: Molecular Cancer (2023)

Skin cancer has emerged as the fifth most commonly reported cancer in the world, causing a burden on global health and the economy. The enormously rising environmental changes, industrialization, and genetic modification have further exacerbated skin cancer statistics. Current treatment modalities such as surgery, radiotherapy, conventional chemotherapy, targeted therapy, and immunotherapy are facing several issues related to cost, toxicity, and bioavailability thereby leading to declined anti-skin cancer therapeutic efficacy and poor patient compliance. In the context of overcoming this limitation, several nanotechnological advancements have been witnessed so far. Among various nanomaterials, nanoparticles have endowed exorbitant advantages by acting as both therapeutic agents and drug carriers for the remarkable treatment of skin cancer. The small size and large surface area to volume ratio of nanoparticles escalate the skin tumor uptake through their leaky vasculature resulting in enhanced therapeutic efficacy. In this context, the present review provides up to date information about different types and pathology of skin cancer, followed by their current treatment modalities and associated drawbacks. Furthermore, it meticulously discusses the role of numerous inorganic, polymer, and lipid-based nanoparticles in skin cancer therapy with subsequent descriptions of their patents and clinical trials.
Dorsomedial prefrontal hypoexcitability underlies lost empathy in frontotemporal dementia
Authors: Hannah L. Phillips, Huihui Dai, So Yoen Choi, Karen Jansen-West, Alexis S. Zajicek, Luke Daly, Leonard Petrucelli, Fen-Biao Gao, Wei-Dong Yao
Journal: Neuron (2023)
ClonoCluster: A method for using clonal origin to inform transcriptome clustering
Authors: Lee P. Richman, Yogesh Goyal, Connie L. Jiang, Arjun Raj
Journal: Cell Genomics (2023)

Clustering cells based on their high-dimensional profiles is an important data reduction process by which researchers infer distinct cellular states. The advent of cellular barcoding, however, provides an alternative means by which to group cells: by their clonal origin. We developed ClonoCluster, a computational method that combines both clone and transcriptome information to create hybrid clusters that weight both kinds of data with a tunable parameter. We generated hybrid clusters across six independent datasets and found that ClonoCluster generated qualitatively different clusters in all cases. The markers of these hybrid clusters were different but had equivalent fidelity to transcriptome-only clusters. The genes most strongly associated with the rearrangements in hybrid clusters were ribosomal function and extracellular matrix genes. We also developed the complementary tool Warp Factor that incorporates clone information in popular 2D visualization techniques like UMAP. Integrating ClonoCluster and Warp Factor revealed biologically relevant markers of cell identity.
Reply: Intrapulmonary shunt and alveolar dead space in a cohort of patients with acute COVID-19 pneumonitis and early recovery
Authors: Piotr Harbut, G. Kim Prisk, Robert Lindwall, Sarah Hamzei, Jenny Palmgren, Catherine E. Farrow, Goran Hedenstierna, Terence C. Amis, Atul Malhotra, Peter D. Wagner, Kristina Kairaitis
Journal: European Respiratory Journal (2023)

We thank M. Ackermann and co-workers for their interest in our recent publication [1]. These authors highlight our report of persistent increased alveolar dead space in 30% of 17 patients studied within ∼2 months after an acute episode of mild–moderate COVID-19. After outlining their own work, demonstrating secondary pulmonary lobule pathologies found in the lungs of deceased COVID-19 patients, they then hypothesise that secondary lobular micro-ischaemia may be responsible for the elevated alveolar dead space found in our study. Increased dead space following COVID-19 may be due to microvascular injury or secondary micro-ischaemia https://bit.ly/3Fypdwz
Intersection of immune and oncometabolic pathways drives cancer hyperprogression during immunotherapy
Authors: Gaopeng Li, Jae Eun Choi, Ilona Kryczek, Yilun Sun, Peng Liao, Shasha Li, Shuang Wei, Sara Grove, Linda Vatan, Reagan Nelson, Grace Schaefer, Steven G. Allen, Kamya Sankar, Leslie A. Fecher, Mishal Mendiratta-Lala, Timothy L. Frankel, Angel Qin, Jessica J. Waninger, Alangoya Tezel, Ajjai Alva, Christopher D. Lao, Nithya Ramnath, Marcin Cieslik, Paul W. Harms, Michael D. Green, Arul M. Chinnaiyan, Weiping Zou
Journal: Cancer Cell (2023)
Vaccination Coverage by Age 24 Months Among Children Born During 2018–2019 — National Immunization Survey–Child, United States, 2019–2021
Authors: Holly A. Hill, Michael Chen, Laurie D. Elam-Evans, David Yankey, James A. Singleton
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Millions of young children are vaccinated safely in the United States each year against a variety of potentially dangerous infectious diseases (1). The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination against 14 diseases during the first 24 months of life* (2). This report describes vaccination coverage by age 24 months using data from the National Immunization Survey-Child (NIS-Child).† Compared with coverage among children born during 2016-2017, coverage among children born during 2018-2019 increased for a majority of recommended vaccines. Coverage was >90% for ≥3 doses of poliovirus vaccine (93.4%), ≥3 doses of hepatitis B vaccine (HepB) (92.7%), ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.6%), and ≥1 dose of varicella vaccine (VAR) (91.1%); coverage was lowest for ≥2 doses of hepatitis A vaccine (HepA) (47.3%). Vaccination coverage overall was similar or higher among children reaching age 24 months during March 2020 or later (during the COVID-19 pandemic) than among those reaching age 24 months before March 2020 (prepandemic); however, coverage with the combined 7-vaccine series§ among children living below the federal poverty level or in rural areas decreased by 4-5 percentage points during the pandemic (3). Among children born during 2018-2019, coverage disparities were observed by race and ethnicity, poverty status, health insurance status, and Metropolitan Statistical Area (MSA) residence. Coverage was typically higher among privately insured children than among children with other insurance or no insurance. Persistent disparities by health insurance status indicate the need to improve access to vaccines through the Vaccines for Children (VFC) program.¶ Providers should review children's histories and recommend needed vaccinations during every clinical encounter and address parental hesitancy to help reduce disparities and ensure that all children are protected from vaccine-preventable diseases.
Magnetic Resonance Imaging–Guided vs Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer
Authors: Amar U. Kishan, Ting Martin Ma, James M. Lamb, Maria Casado, Holly Wilhalme, Daniel A. Low, Ke Sheng, Sahil Sharma, Nicholas G. Nickols, Jonathan Pham, Yingli Yang, Yu Gao, John Neylon, Vincent Basehart, Minsong Cao, Michael L. Steinberg
Journal: JAMA Oncology (2023)

Magnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial.
Incidence, Timing, and Factors Associated With Suicide Among Patients Undergoing Surgery for Cancer in the US
Authors: Alexandra L. Potter, Chinmay Haridas, Krista Neumann, Mathew V. Kiang, Zhi Ven Fong, Corinne A. Riddell, Harrison G. Pope, Chi-Fu Jeffrey Yang
Journal: JAMA Oncology (2023)

The risk and timing of suicide among patients who undergo surgery for cancer remain largely unknown, and, to our knowledge, there are currently no organized programs in place to implement regular suicide screening among this patient population.
The MIRAGE Trial—Optical Illusion or the Future of Prostate Stereotactic Radiotherapy?
Authors: Shankar Siva, Piet Ost, Muhammad Ali
Journal: JAMA Oncology (2023)

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Ethylene oxide emissions and incident breast cancer and non-Hodgkin lymphoma in a US cohort
Authors: Rena R Jones, Jared A Fisher, Danielle N Medgyesi, Ian D Buller, Linda M Liao, Gretchen Gierach, Mary H Ward, Debra T Silverman
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Ethylene oxide (EtO) is a carcinogenic gas used in chemical production and to sterilize medical equipment that has been linked to risk of breast and lymphohematopoietic cancers in a small number of occupational studies. We investigated the relationship between environmental EtO exposure and risk of these cancers. Methods Using the US Environmental Protection Agency’s Toxics Release Inventory, we estimated historical exposures for National Institutes of Health–AARP Diet and Health Study participants enrolled in 1995-1996. We constructed 2 metrics at 3, 5, and 10 km: 1) distance between residences and EtO-emitting facilities, weighted by the proportion of time the home was downwind of each facility, and 2) distance-weighted, wind direction–adjusted average airborne emissions index (AEI=∑[lbs EtO/km2]). We estimated risk (hazard ratio [HR], 95% confidence interval [CI]) of incident breast cancer (in situ and invasive) among postmenopausal women (n = 173 670) overall and by tumor estrogen receptor status and non-Hodgkin lymphoma in the full cohort (n = 451 945). Results We observed an increased risk of breast cancer associated with EtO-emitting facilities within 10 km (HR[≤10vs&amp;gt;10] = 1.05, 95% CI = 1.00 to 1.10) that appeared stronger for in situ (HR[≤10vs&amp;gt;10] = 1.13, 95% CI = 1.00 to 1.27) than invasive (HR[≤10vs&amp;gt;10] = 1.03, 95% CI = 0.97 to 1.09) disease. Risk of breast cancer in situ was also increased in the top AEI quartiles, and associations weakened with larger distances (HR[Q4vs0] = 1.60, 95% CI = 0.98 to 2.61; HR[Q4vs0] = 1.28, 95% CI = 0.92 to 1.79; HR[Q4vs0] = 1.25, 95% CI = 1.02 to 1.53 at 3, 5, and 10 km, respectively). No differences in breast cancer risk were observed by estrogen receptor status. We found no clear pattern of increased non-Hodgkin lymphoma risk. Conclusions A novel potential association between EtO emissions and risk of in situ, but not invasive, breast cancer warrants additional evaluation.
A transdiagnostic network for psychiatric illness derived from atrophy and lesions
Authors: Joseph J. Taylor, Christopher Lin, Daniel Talmasov, Michael A. Ferguson, Frederic L. W. V. J. Schaper, Jing Jiang, Madeleine Goodkind, Jordan Grafman, Amit Etkin, Shan H. Siddiqi, Michael D. Fox
Journal: Nature Human Behaviour (2023)